Pneumocystis carinii (Pc) is an important and potentially lethal pulmonary pathogen in many immuno-compromised individuals, most notably those with the Acquired Immunodeficiency Syndrome (AIDS). Over 80% of individuals with AIDS will develop Pc pneumonitis or pneumonia (PCP) over the course of their lives without specific antibiotic prophylaxis. PCP is the most significant immediate cause of death in AIDS. PCP is also a serious complication in cancer and transplant patients and malnourished children. (Hughes, W. T., Pneumocystis carinii Pneumonitis, New York: CRC Press, 1987; Kovacs, J. A. et al. (1984) Annals of Internal Medicine 100:663-671; Murray, J. F. et al. (1984) New England J. Med. 310:1682-1688; Goedert, J. J. et al. (1987) JAMA 257(3):331-4; Bonagura, V. R. et al. (1989) Clin. Immun. Immunopath. 51(2):216-31; Mamedov, N. A. et al. (1991) Mikrobiol. Epidemiol. Immunobiol. 0(2);32-34; Maddison, S. E. et al. (1982) J. Clin. Microbiol. 15(6):1029-1035; Jarowenko, M. et al. (1986) Transplantation 41(4):436-442)
Standard prophytaxis with trimethoprim-sulfamethoxazole (TMP-SMX), pentamidine, isethionate, Dapsone and other newer modalities have reduced the mortality and morbidity due to PCP. However, therapy with these agents is frequently attended by adverse reactions, such as allergic reactions, to these drugs. Most notably, over half of patients with AIDS will have adverse reactions to one or more of these agents. This has limited the utility of both prophylactic agents and therapies in the treatment of PCP in the AIDS patients. In transplant patients, synergistic toxicity to the kidneys has been observed between TMP-SMX and the immunosuppressive drugs cyclosporin A and azathioprine. (Fishman, J. A., Medical Times, 1989, pp. 21-34; Fishman, J. A., Pulmonary Diseases and Disorders. In: Pneumocystis carinii Pneumonitis (A. P. Fishman, ed.). New York: McGraw Hill, 1991, in press; Masur, H. (1989) J. Protozoology 36(1):70-74; Matsumoto, Y. et al. (1991) Abstract WS1, Program and Abstracts of the 44th Annual Meeting of the Society of Protozoologists, Jun. 28-Jul. 2, 1991:46) It has been stated that: "Under these circumstances, an understanding of pneumocystosis is urgent and basic studies of this organism are necessary" (Nakamura, Y. et al. (1989) 36(1):58S-60S).
However, studies of the pathogenesis of PCP have been hindered by the absence of a continuous culture system for the growth of human or animal Pc, and by the contamination of Pc preparations by host proteins and nucleic acids. Despite some improvements in both the animal and tissue culture systems for the growth and purification of Pc, dissection of the interactions of Pc with the cells and tissues and the immune system of the host has been difficult. (Bartlett, M. S. et al. (1988) J. Clin. Microbiol. 26:1100-1102)